Physostigmine plant-derived alkaloids

Carbamate Insecticides. These are stmcturaUy optimi2ed derivatives of the unique plant alkaloid physostigmine [57-47-6] a cholinergic dmg isolated in 1864 from Phjsostigma venenosum (see Alkaloids) (17,24,35—39). The carbamates maybe considered synthetic derivatives of the synaptic neurotransmitter acetylcholine, with very low turnover numbers. The A/,A/-dimethylcarbamates of heterocycHc enols (36) and the Ai-methylcarbamates of a variety of substituted phenols (35) with a wide range of insecticidal activity were described in 1954 (35). The latter are the most widely used carbamate insecticides, and the A/-methylcatbamates of oximes have subsequentiy been found to be effective systemic insecticides. 

The proof of structure of dehydroesermetholemethine gave considerable further support to the 3a-methylpyrrolo[2,3-6]indole structure for physostigmine proposed by Robinson. The Robinson structure for the alkaloid also was derived easily from tryptophan, thus offering an obvious biogenetic route of synthesis by the plant (this will be discussed in more detail later). 

Despite the fact that physostigmine is an important pharmaceutical, no reports have appeared on efforts to produce this alkaloid by means of plant cell cultures. Daoust (737) reported the fermentative production of physostigmine by means of the microorganism Streptomyces griseofuscus. Iwasa et al. (738) employed Streptomyces pseudogriseo-lus for the production of physostigmine. Murao and Hayashi (739) isolated physostigmine and its N-8 nor derivative from Streptomyces sp. AH-4. 

Following the successful isolation of morphine (1805), attention turned to a number of other prominent traditional medicines or toxic plants in order to derive their active principles. Many of these active compounds were alkaloids.They include the important alkaloids emetine (1816),strychnine (1818), quinine (1820), colchicine (1820), caffeine (1820), nicotine (1828), atropine (1833), cocaine (1860), physostigmine (1864), and ephed-rine (1887). Therefore, it is important to understand and appreciate the significance of alkaloids as the source of medicines, direcdy and indirecdy through structure modification. 

While phenyl pyrrole derivatives have not been isolated from higher plants, a number of plant alkaloids have been shown to be derived from tryptophan (Manske, 1965). Several of these plants, such as the calabar bean (Physostigma venenosum Balf.) and the family Calycanthaceae [Calycanthus L. and Chimonanthus Lindl.), yield compounds, e.g. physostigmine (VIII) and folicanthine (IX) whose biosynthesis may follow a pathway similar to that of pyrrolnitrin. 

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